kvlevebis roli TB globaluri gegmis

SesrulebaSi

neli solomonia, “samSabaToba”, 19.10.10

http://www.newtbdrugs.org/rsvp.php

Friday, November 12, 2010, 7:30am-1:00pm

The Kempinski Hotel Bristol Berlin, http://www.kempinski-berlin.de/en/hotel/

NEW DIAGNOSTICS WORKING GROUP ANNUAL MEETING

The Stop TB Partnership New Diagnostics Working Group will hold its annual meeting in Berlin, Germany, in conjunction with the 41st Union World Conference on Lung Health.

Thursday, 11th November 201013:00-17:00International Congress Center, Berlin, Hall 7

http://www.stoptb.org/wg/new_diagnostics/#

fundamenturi kvlevebi:

adamianis organizmSi M. tuberculosis moqmedebis paTomorfologiuri meqanizmis srulyofili Seswavla;

gansxvavebuli imunokompetenciis mqone individebSi specifiuri imunuri pasuxis Taviseburebebis Seswavla;

LTBI-is aqtiur TB-Si gadasvlis meqanizmis sworad gansazRvra; maRalsensitiuri meTodebis SemuSaveba qsovilSi mikobaqteriis

upiratesi lokalizaciis meqanizmis da im korelaciis gansazRvrisaTvis, romelic arsebobs mikobaqteriis ricxvs/formasa da daavadebis fazas/gamosavals Soris;

rogoria qsovilSi specifiuri cvlilebebis mimdinareoba da rogoria paTfiziologiuri cvlilebebis gavlena TB daavadebis dinamikaze;

maRalsensitiuri meTodologiis SemuSaveba molekulur doneze mikobaqteriis, pacientis da TB preparatebis urTierTqmedebis srulyofilad gaSifrisaTvis, mikobaqteriis sasicocxlo ciklSi yvelaze faqizi etapis gansazRvra misi maqsimalurad efeqturi eliminaciisaTvis;

ramdenad gansxvavebulia mikobaqteriis genomi individis, geografiuli arealis, an globalur populaciaSi;

TB kvlevebSi yvela saWiro samecniero disciplinebis wamyvani mecnierebis/laboratoriebis CarTva;

ZiriTadi aqcentebi:

• ukve arsebuli da axali preparatebis kombinaciiT DS/DR-TB mkurnalobis xangrZlivobis Semcireba;

• M/XDR-TB axali samkurnalo preparatebis Seqmna;

• HIV/AIDS-TB ko-infeqciis maqsimaluri efeqturobiT marTva;

• LTBI-is da bavSvTa tuberkulozis mkurnaloba.

REMoxTB

DS-TB mkurnalobaSi Mfx-is H-iT an E-iT CanacvlebiT mkurnalobis xangrZlivobis

6-dan 4 Tvemde Seamcireba 6H+R+E+Z 4Mfx+R+E+Z an 4Mfx+H+R+Z;Mfx naklebad axdens citoqrom P-450

fermentis inducirebas, amitom misi gamoyeneba SeiZleba ARV mkurnalobis pirobebSi;

H-is Mfx-iT Canacvleba TB maRali tvirTis mqone qveynebSic SesaZlebels gaxdis LTBI-s H-iT mkurnalobas.

http://www.tballiance.org/downloads/publications/TBA%20Annual%202009.pdf

mkurnalobis xangrZlivobis Semcireba gazrdis mkurnalobisadmi damyolobas, Seamcirebs wyvetili mkurnalobis SemTxvevebs;

fasis miuxedavad Mfx-is gamoyeneba xarjefeqturia;

uaryofiTi mxareebi: saqarTveloSi maRalia qinolonebis mimarT

jvaredini pirveladi rezistentobis arsebobis albaToba;

Mfx-is gamoyenebas Tan axlavs toqsiuri gverdiTi movlenebi;

Mfx-is gamoyeneba ar SeiZleba bavSvebSi.

Historic Opportunity to Develop New Therapeutic Options for TB

1950 2010

1952 1st regimen:

• Streptomycin• PAS• Isoniazid

1963 Rifampin

(RIF) discovered

1970BMRC Trials

add RIF

1974 BMRC Trials add

RIF & PZA 2005 Trials substitute

Moxifloxacin into regimen

19701960

1954Pyrazainimide

(PZA) discovered – but liver

toxicity

Rx lasts from 12-24 months

Rx shortened to 9 months

Rx shortened to 6 months

Rx target: 3-4 months

Standard Therapy 2 months: rifampin, isoniazid,

pyrazinamide, ethambutol +

4 months: rifampin, isoniazid

Standard Regimen by 1960s based on 1952 drugs

1980

In an animal study*, moxifloxacin regimen shortened treatment duration by 2 months

0123456789

10

0 1 2 3 4 5 6

Duration of treatment (months)

Log

CFU

in e

ntire

lung

Untreated

2 months rifampin, isoniazid and pyrazinimide followed by 4 months rifampin and isoniazid

2 months rifampin, moxifloxacin and pyrazinimide followed by 4 months rifampin and moxifloxacin

*In vivo data does not predict clinical response.

Legend

TMC-207 dairqinolonebis jgufis preparati; mikobaqteriis garsis warmoqmnis

energetikuli wyaros - specifiuri atf-sinTetazas inhibitori;

Zlieri baqteriociduli da masterizebeli moqmedeba axasiaTebs rogorc DR-, ise DS-TB Stamze;

PA-824: uaxlesi antibaqteriuli preparatebis jgufi; nitroimidazoli:

aqvs baqteriociduli da masterizebeli moqmedeba; efqturia rogorc sensitiuri, ise rezistentuli TB-s

samkurnalod; SeiZleba ARV TerapiasTan kombinaciaSi gamoyeneba; 2005 wlidan CarTulia preklinikuri kvlevebis I stadiaSi.

abebis alternativa – PTB-is sainhalacio formiT mkurnaloba

• kvlevebi mimdinareobs PA-824-is sainhalacio formis danergvis mizniT;

• klinikuri kvlevebi Catarda zRvis gowebze – erTmanets Sedarda 40 mg/kg oraluri, 4.8 mg/kg da 9.7 mg/kg sainhalacio forma da placebo;

• orive dozis sainhalacio forma plazmaSi maqsimalur koncentracias aRwevs 3-4 ssaTSi da organizmSi cirkulirebs inhalaciidan 24 sT-is ganmavlobaSi

preparatebi, romlebzeac mimdinareobs kvlevebi

Critical Path to TB Regimens (CPTR) will drastically reduce the amount of time needed to register novel regimens for tuberculosis and drug-resistant tuberculosis from decades to years.

http://www.tballiance.org/cptr/

• Vaccine update • Aeras and Crucell launch vaccine trial in Kenya • In September, Dutch biopharmaceutical company Crucell N.V. and the Aeras

Global TB Vaccine Foundation announced the start of a Phase II clinical trial in infants of the jointly developed TB vaccine candidate, AERAS-402/Crucell Ad35.

• The main objective of the trial is to test the safety and efficacy of the TB vaccine candidate in infants previously vaccinated with the Bacille Calmette-Guérin (BCG) vaccine. The first part of this clinical trial, which will be conducted in Kenya, will establish the optimal dosing regimen. The selected regimen will then be tested in the second part of the trial, which is planned to begin in 2011 in Kenya, Mozambique, South Africa and Uganda.

• AERAS-402/Crucell Ad35 busteria da adenovirus 35 veqtoriT iwvevs M. tuberculosis 85A, 85B, TB10.4 antigenebis eqspresias, rac TavisTavad CD+4 da CD+8 markeris mqone T limfocitebis inducirebas axdens;

http://www.aeras.org/newscenter/news-detail.php?id=1043

• Vaccine update • Clinical trial of new investigational vaccine AERAS-422• At the Second Global Forum on TB Vaccine Development in

Tallinn, Estonia in September (see "Recent Events", below), the Aeras Global TB Vaccine Foundation announced that it will initiate a clinical trial of an investigational live recombinant tuberculosis vaccine to be led by researchers at Saint Louis University in St. Louis, Missouri, USA.

• AERAS-422 BCG vaqcinis rekombinanti, anu modernizebuli versiaa da Seiqmna pirveladi inficirebis, LTBI-is da LTBI-is reaqtivaciis prevenciis mizniT;

http://www.aeras.org/newscenter/news-detail.php?id=1044

TB pandemiis winaaRmdeg BCG araefeqturi aRmoCnda

• BCG bavSvs mxolod TB diseminirebuli formebis da TB meningitis ganviTarebisagan icavs;

• BCG ver icavs organizms LTBI-isagan;• BCG aiv-inficirebuli CvilebisaTvis maRal risks

warmoadgens (yovel 100 000 mosaxleze aivinficirebulTa 992 SemTxvevaSi BCG-irebam TB diseminirebuli formebis ganviTareba gamoiwvia (World Health Organization; Type: Research Article DOI: 10.2471/BLT.08.055657 2009-janmo iZleva rekomendacias aiv testirebis gareSe Cvilebis BCG-ireba ar Catardes; - 02.07.09; WHO).

axali TB vaqcinis aucilebloba TB globaluri miznis miRweva (>1 TB SemTx./milion

mosaxleze) axali vaqcinis, anu daavadebis prevenciis gareSe SeuZlebelia;

aucilebelia TB axali, ekonomiuri, efeqturi vaqcina, romelic saimedod daicavs:

nebismieri asakis organizms; maT Soris HIV-inficirebulebs;da uzrunvelyofs: LTBI_is prevencias (preinfeqciuri vaqcinacia); LTBI-is reaqtivaciis prevencias (postinfeqciuri

vaqcinacia); TB pirveladi da meoradi, maT Soris MDR/XDR formebis

prevencias; TB mkurnalobis xangrZlivobis Semcirebas da TB

mkurnalobis efeqturobis zrdas (imunoTerapia).

Block Initial Infection

Prevent Early Disease

Prevent LatentInfection

Prevent Reactivation

Disease

operaciuli kvlevebi:

epidmdgomareobis statistikuri Sefasebidan

TB diagnostikis; mkurnalobis; klinikuri mimdinareobis

kompleqsuri gaanalizebisa

TB srulyofili marTvisaken

rogorc yovelTvis

didi madloba

yuradRebisaTvis